The nuclear factor κB (NF-κB)-related disorders encompassed not only common variable immunodeficiency but also manifestations of autoinflammation, autoimmunity, and malignancies. While most cases have been reported in European populations, reports in the Chinese population are sparse. Clinical data and genetic variants from four Chinese patients with NFKB1 variants, alongside four previously reported cases, were analyzed and compared with an international cohort. Additionally, comprehensive in vitro functional assays-including immunoblotting, transcript analyses, dual-luciferase reporter, and co-immunoprecipitation assays-were conducted to explore the molecular defects of the novel variants. Our cohort included three men and one woman, all presenting with recurrent fever and hypogammaglobulinemia. Three patients experienced recurrent sinopulmonary infections, accompanied by decreased B cells and NK cells, while two patients developed pneumonia, bronchiectasis, and hepatitis. Three novel NFKB1 (NM_003998) variants were identified: c.559C > T (p. Arg187Trp), c.1509del (p. Glu504Argfs*19), and c.1753-11_1760del (p. Thr585Alafs*9). Functional analyses revealed distinct pathomechanisms: the frameshift/splicing variants drive classical haploinsufficiency via nonsense-mediated mRNA decay (NMD), triggering compensatory inflammatory hyperactivation; conversely, the p.Arg187Trp missense variant maintains protein stability and heterodimerization but strictly abolishes DNA-binding capacity. Compared to a previously reported cohort, Chinese patients were predominantly male, had a later median age of onset and diagnosis. Notably, Chinese patients exhibited a higher prevalence of hepatitis (25%) and cirrhosis (12.5%), potentially reflecting the high endemicity of hepatitis B virus in China. They also showed increased rates of viral infections, sepsis, and bronchiectasis, with more pronounced reductions in NK and B cells. In contrast, autoimmune diseases and bronchitis were less frequent than in the foreign cohort. This study represents the first and largest case series of Chinese patients with NF-κB1-related diseases, providing molecular characterization for three novel variants. In this limited case series, the observed delayed onset and frequent hepatic complications in our cohort may reflect regional factors, such as HBV endemicity, or ascertainment bias. Our findings underscore that suspected AOSD accompanied by hypogammaglobulinemia warrants immediate genetic investigation. Early diagnosis is essential to prioritize immunoglobulin replacement and prevent fatal complications from immunosuppressive therapy.

Idiopathic multicentric Castleman disease (iMCD) is a rare disease characterized by polyclonal lymphoproliferation and systemic inflammation. Siltuximab, targeting interleukin-6 (IL-6), has been recommended as the first-line therapy for iMCD. However, substantial real-world data from China were still lacking, and treatment for patients with severe iMCD remained challenging. This single-center retrospective study investigated the real-world efficacy and safety of siltuximab-based therapy in 43 consecutive patients with iMCD in China from July 2022 to March 2024. The overall response rate (including symptomatic and biochemical response) was 59

Background： Peripheral T-cell lymphoma (PTCL) comprises a group of heterogeneous and aggressive non-Hodgkin lymphomas associated with poor outcomes. CHOP remains the standard first-line therapy, yet the 5-year overall survival (OS) remains suboptimal. Golidocitinib, a potent and selective JAK1 inhibitor, has demonstrated promising anti-tumor activity with favorable safety profile in relapsed/refractory (r/r) PTCL. Aims： To evaluate the anti-tumor activity and tolerability of Golidocitinib in combination with CHOP regimen (Go-CHOP) as the frontline therapy for patients with PTCL. Methods： This is an ongoing phase 1/2, single-center, single-arm clinical trial (NCT06739265) evaluating Go-CHOP as first-line therapy in adults patients (≥18 years) with histologically confirmed, previously untreated PTCL, including PTCL-not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic large cell lymphoma (ALCL), etc. The study consists of two sequential phases: a 3+3 dose-escalation cohort (Phase 1) to determine the recommended phase 2 combination dose (RP2CD), followed by a dose-expansion cohort (Phase 2) assessing efficacy and safety. In Phase 1, patients receive six 21-day cycles of Go-CHOP: oral golidocitinib 150 mg every other day (Qod) on days 1-21 combined with standard CHOP chemotherapy (cyclophosphamide 750 mg/m², doxorubicin 50 mg/m², vincristine 1.4 mg/m² IV on day 1, and prednisone 100 mg po on days 1-5). Dose escalation to 150 mg once daily was permited if ≤1/6 patients experienced dose-limiting toxicities (DLTs) during cycle 1, defined as grade 4 hematological toxicity lasting ≥7 days or grade ≥3 non-hematological events (per CTCAE v5.0). In Phase 2, patients received Go-CHOP at the RP2CD. Interim PET-CT was performed after 3 cycles. Responders at the end of Go-CHOP therapy received either consolidative autologous stem cell transplantation (ASCT), if eligible, or golidocitinib maintenance for transplant ineligible patients for up to 24 months or until disease progression or unacceptable toxicity. The primary endpoint is complete response rate (CRR) assessed according to the Lugano 2014 criteria, at the end of Go-CHOP therapy. Results： As of the data cutoff on August 3rd, 2025, eighteen patients were enrolled and received at least one cycle of Go-CHOP regimen, including 6 patients in phase 1 and 12 patients in phase 2. The median age was 50 years (range, 18-70), and 14 patients (77.8%) were male. All eighteen patients (100%) had stage III-IV disease, and eleven (61.1%) had an IPI score of 3-5. Diagnoses included: AITL in 9 patients (50%), PTCL-NOS in 7 (38.9%), MEITL in 1 (5.6%), and ALK+ALCL in 1 (5.6%). No DLTs were observed in the dose escalation phase, establishing 150 mg golidocitinib once daily as RP2CD. Treatment-related adverse events (TRAEs) were observed in 17 patients (94.4%), with neutropenia being the most common one (72.2%), followed by urinary tract infection (22.2%) and thrombocytopenia (22.2%). Grade 3/4 TRAEs were primarily neutropenia, observed in 61.1% of the patients. CMV reactivation was observed in 3 patients (16.6%) and warrants close monitoring. Additionally, one case of hepatitis B virus reactivation and one case of pulmonary cryptococcosis were reported, the latter resulting in treatment discontinuation. One fatal case of gastrointestinal bleeding was reported, which was assessed as unrelated to the treatment by the investigator. Among 15 efficacy-evaluable patients, 12 achieved objective responses, and 11 reached CR, yielding an overall response rate (ORR) of 80.0% and a CRR of 73.3%. With a median follow-up of 5.5 months, the median progression-free survival and OS will be reported after longer follow-up. Conclusion: Preliminary results of golidocitinib in combination with CHOP demonstrated a manageable safety profile and encouraging antitumor activity in newly diagnosed PTCL. This clinical trial is ongoing.

Abstract Background: Emerging evidence suggests that triple-combination regimens incorporating Bruton tyrosine kinase (BTK) inhibitors, CD20-targeted agents, and immunomodulatory drugs (e.g., lenalidomide) may exhibit promising antitumor activity in indolent B-cell non-Hodgkin lymphomas (B-NHLs). In this study, we evaluated the efficacy and safety of orelabrutinib plus obinutuzumab and lenalidomide(GOL regimen) as a first-line therapy for MZL patients, aiming to assess its potential as a chemotherapy-free treatment option. Methods: In this prospective single-arm multicenter phase II trial (NCT06454968), eligible treatment-naïve adults (≥18 years) with histologically confirmed marginal zone lymphoma requiring systemic therapy received six 21-day cycles of induction therapy (oral orelabrutinib 150 mg QD on days 1-21, intravenous obinutuzumab 1000 mg on day 1 of each cycle, and oral lenalidomide 25 mg QD on days 1-14) followed by six 28-day cycles of orelabrutinib monotherapy (150 mg QD). The primary endpoint of our study is complete response rate, secondary endpoints were overall response rate, duration of response, uMRD rate of SMZL by IgH-DNA sequencing, and safety. Results: As of August 1, 2025, a total of 23 patients were enrolled in the study. The median age was 60 years (range: 36-81) with a male-to-female ratio of 0.92:1. Subtype distribution included: MALT/EMZL (n=9, 39.1%), SMZL (n=9, 39.1%), and dissMZL (n=5, 21.8%). All patients had Ann Arbor stage IV disease, with 6 cases (26.1%) presenting B symptoms. The MZL-IPI score distribution was: 0 points in 6 cases (26.1%), 1-2 points in 14 cases (60.9%), and 3-5 points in 3 cases (13.0%). Monoclonal gammopathy was observed in 9 out of 19 evaluable patients. All splenic marginal zone lymphoma (SMZL) patients exhibited massive splenomegaly, with 4 out of 9 showing baseline leukocytosis (peak WBC count 387.5×10⁹/L, lymphocyte count 371.9×10⁹/L). To date, 10 patients have completed 6 cycles of the three-drug combination (GOL) regimen, while 5 patients have completed all treatment and entered the follow-up phase. Among 18 response-evaluable patients, the overall response rate (ORR) was 88.9% (16/18) and the complete response rate (CRR) was 72.2% (13/18). By subtype analysis:SMZL patients demonstrated excellent outcomes with 100% ORR (6/6) and 100% CRR (6/6), all achieving complete remission by cycle 3, including 5 cases (83.3%) attaining MRD negativity by IgH-DNA sequencing;MALT/EMZL patients showed 77.8% ORR (7/9) and 66.7% CRR (6/9);dissMZL patients achieved 100% ORR (3/3) but a lower CRR of 33.3% (1/3). With a median follow-up of 8.1 months (range 2.3-13.1 months), none of the responding patients experienced disease progression, and the median duration of response (DOR) has not been reached. Regarding safety, all-grade adverse events included: infusion-related reactions (6/23), thrombocytopenia (6/23), rash (5/23), herpes zoster (2/23), petechiae (2/23), leukopenia (1/23), influenza A pneumonia (1/23), and invasive pulmonary aspergillosis (1/23). Grade 3 adverse events were limited to infusion-related reactions (2/23), thrombocytopenia (2/23), and rash (2/23), with no grade 4-5 adverse events reported. Conclusion: This phase II study demonstrates that the novel triple-combination regimen shows promising efficacy in treatment-naïve MZL patients, with an impressive overall response rate (88.9%) and complete response rate (72.2%), particularly in SMZL patients who achieved 100% CR. The regimen exhibited a manageable safety profile with no grade 4-5 adverse events. Early MRD negativity in SMZL suggests potential for durable remissions. These results support further study of this chemotherapy-free approach.

A novel, highly purified 10% intravenous immunoglobulin (IVIG) formulation was evaluated for both therapeutic efficacy and safety profile in adult patients diagnosed with persistent or chronic primary immune thrombocytopenia (ITP). This phase III, multicenter, open-label, single-arm clinical trial enrolled Chinese adult patients diagnosed with persistent or chronic ITP presenting with baseline platelet counts below 30 × 109/L. Participants received intravenous administration of 10% IVIG at a standardized dosage of 1 g/kg/day for two consecutive days. The primary efficacy endpoint was defined as the proportion of subjects achieving both a platelet count elevation to ≥ 30 × 109/L and a minimum two-fold increase from baseline values within a 7-day post-treatment observation period following the first dose administration. Seventy-two patients were enrolled and sixty patients completed the study. 52 (72.2%; 95% CI: 60.4, 82.1) patients achieved platelet count ≥ 30 × 109/L and experienced a ≥ twofold increase from baseline within 7 days, and 52 (72.2%; 95% CI: 60.4, 82.1) patients achieved complete response (CR) or response (R) within 7 days. 64 patients (88.9%; 95% CI: 79.3, 95.1) achieved platelet count ≥ 50 × 109/L within 7 days with a median time of 3 days. 71 patients completed the ITP bleeding scale assessment after 7 days, showing a decrease of 0.6 ± 1.07 from baseline. A total of 66 patients (91.7%) reported treatment-emergent adverse events (TEAEs) during the study, and 37 patients (51.4%) reported adverse drug reactions (ADRs). The most prevalent ADRs with an incidence exceeding 5% included headache (n = 12, 16.7%), fever (n = 10, 13.9%), decreased white blood cell count (n = 5, 6.9%), and nausea (n = 5, 6.9%). The therapeutic regimen of 10% IVIG administered at a dosage of 1 g/kg/day for two consecutive days demonstrated both favorable safety profiles and clinical efficacy. These robust findings provide substantial evidence supporting the clinical application of this novel 10% IVIG formulation in the management of adult patients with ITP.

Introduction: The regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) remains the standard first-line treatment for diffuse large B-cell lymphoma (DLBCL), yet many patients relapse. Polatuzumab vedotin combined with rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) has shown promise in trials. This study investigates the real-world efficacy and safety of Pola-R-CHP versus R-CHOP. Methods: We retrospectively analyzed 505 DLBCL patients treated at Peking Union Medical College Hospital between January 2011 and March 2025. Thirty-six patients received Pola-R-CHP; 36 matched R-CHOP patients were selected using 1:1 propensity score matching based on age, sex, subtype, stage, and IPI. Outcomes included interim and end-of-treatment response, overall survival (OS), progression-free survival (PFS), and adverse events (AEs). Results: Post-matching, 72 patients were included. Pola-R-CHP achieved higher interim complete response (CR) (72.2% vs. 63.9%, p = 0.035) and objective response rate (ORR) (100.0% vs. 83.3%, p = 0.011). At the end of treatment, CR was further improved (88.9% vs. 63.9%, p = 0.007), and ORR remained superior (100.0% vs. 86.1%, p = 0.020). At a median follow-up of 13.3 months (range, 1.1–141.9 months), 1 death and 2 progressions occurred in the Pola-R-CHP group compared with 9 deaths and 9 progressions in the R-CHOP group. Median OS and PFS were not reached in either cohort. At 12 months, the estimated OS was 97% for Pola-R-CHP and 94% for R-CHOP (p = 0.825), while the estimated PFS was 86% and 94%, respectively. This represented a numerical but not statistically significant difference (p = 0.457), likely reflecting the immature survival data and limited number of events at the time of analysis, rather than a true efficacy difference. Neutropenia was the most frequent AE (69.4%) and showed comparable severity between groups, while grades ≥3 AEs were numerically less frequent with Pola-R-CHP (8.3% vs. 13.9%, p = 0.453). Conclusion: Pola-R-CHP achieved higher interim and end-of-treatment response rates than R-CHOP with a comparable safety profile. However, survival outcomes remain immature, and given the small matched sample size (n = 72), these findings should be interpreted cautiously and confirmed in larger prospective studies.

Introductions: Idiopathic multicentric Castleman disease (iMCD) accounts for a significant portion of Castleman disease (CD) cases, presenting with systemic lymphadenopathy, constitutional inflammatory symptoms, polyclonal lymphoproliferation, and multiple organ system dysfunction. It is predominantly driven by a cytokine storm, with interleukin-6 (IL-6) being the key mediator. Consequently, siltuximab, which targets IL-6 directly, is recommended by the Castleman Disease Collaborative Network (CDCN) as a first-line treatment for iMCD, showing high response rates in non-severe iMCD patients. Severe iMCD patients encounter more aggressive cytokine storms, thus requiring more intensive interventions, such as the combination of siltuximab with high-dose steroids. However, substantial real-world data on the use of siltuximab in China were lacking, and treatment for patients with severe iMCD remains challenging. Following the approval of siltuximab by the National Medical Products Administration in December 2021 and its subsequent commercial availability in China in July 2022, we initiated the first real-world retrospective study to focus on the effectiveness and safety of siltuximab in Chinese patients with iMCD, offering crucial real-world insights. Methods: This single-center, retrospective study was conducted at the Peking Union Medical College Hospital, involving iMCD patients treated with siltuximab from July 2022 to March 2024. The diagnostic criteria for iMCD were as follows (CDCN criteria): 1) histopathologic lymph node features consistent with the iMCD spectrum, 2) enlarged lymph nodes in two or more lymph node stations, and 3) satisfying at least two of 11 criteria including one laboratory criterion as proposed by the CDCN and failing to satisfy any of the CDCN's suggested exclusion criterion. Patients were classified into iMCD-TAFRO and iMCD-NOS based on specific diagnostic criteria. Disease severity was categorized according to the CDCN consensus. Treatment response was evaluated as per the CDCN consensus guidelines and the overall response was defined as the symptomatic and biochemical response, except for the lymph node response in imaging. Demographic, clinical, and laboratory data, and treatment options were extracted from medical records. Follow-up data were collected from medical record systems and phone contacts. Study endpoints include overall response rates at Weeks 3, 6, 9, and 12 and adverse events during the treatment and follow-up periods. Fisher's exact test and Student's t-test were used to compare dichotomous variables and continuous variables, respectively. Univariate logistic regression was performed to analyze the potential factors for treatment response. Results: This single-center retrospective study included 43 iMCD patients in China, with a median follow-up time of 4.6 months (range: 1.5-9.5 months). The median age at the initiation of siltuximab was 42 years (range: 15-70 years), and 51.2% of the patients were men (n = 22). Severe iMCD was observed in 20 patients (46.5%). The overall response rate (including symptomatic and biochemical response) was 59% at week 3 and increased to 91% at week 12, with complete and partial response rates of 54% and 37%, respectively. Patients who received siltuximab as a first-line treatment exhibited better treatment response (OR = 0.040, 95% CI, 0.004-0.390, p=0.006). Inflammatory markers (such as IL-6 and high-sensitivity C-reactive protein [hsCRP]) and pathologic types showed no predictive role in the treatment responses. Eighteen patients, who were all classified as severe iMCD, received combined therapy with bortezomib, cyclophosphamide, and dexamethasone (BCD); of them, the overall response rate was 50% at week 3, which increased to 100% at week 12. During the follow-up, adverse reactions included mild skin-related reactions (grade 1 or 2) in three patients, and severe pneumonia (grade 3) in one patient. Conclusions: The study reinforced the existing evidence regarding the efficacy and safety of siltuximab in treating iMCD and underscored the remarkable effectiveness of the combination therapy of siltuximab with the BCD regimen, especially for patients with severe iMCD.

Background:Dysregulated host response is an important cause of critical illness. Coagulation reaction is the most primitive response and can be used to assess patient status. Coagulation reactions may be amplified in very old patients (VOPs). This study aimed to demonstrate coagulation reactions in critically ill VOPs by linking cytokines, coagulation, and fibrinolytic processes. Methods:We analyzed 33 critically ill VOPs admitted to our hospital, with an average age of 91.97. Laboratory test results were collected and double checked. In-hospital mortality, Intensive Care Unit (ICU) stay, and length of in-hospital stay (LOS)-associated variables were assessed using a generalized additive mix model. Smooth curves and interaction tests were used to quantify statistical interactions. Results:The in-hospital mortality rate was 45.5% in this study. The D-dimer level was correlated with ICU stay [risk ratio (RR), 1.39; 95% confidential interval (CI), 1.16-1.67] and LOS (RR, 1.75; 95% CI, 1.19-2.57). Other function or quantity indices, such as platelet (PLT), prothrombin time (PT), activated partial prothrombin time (APTT), and thrombomodulin (TM), were all correlated with clinical outcomes. After the link between coagulation reaction and the outcomes was constructed, it was revealed that, compared to lower level of IL-6, under high level of IL-6, elevated TM was likely to be associated with tissue plasminogen activator inhibitor complex (t-PAIC) elevation, which probably promoted the production of D-dimer (RR, 3.216; 95% CI, 1.840-4.592). Conclusion:D-dimer levels are associated with outcomes in VOPs with critical illness. There is a certain link between inflammatory cytokines and the coagulation process. Under high IL-6 levels, the elevated TM may contribute to the increased t-PAIC, which contributes to the higher D-dimer level. Conversely, under low IL-6 levels, elevated TM levels are associated with reduced t-PAIC levels.

Introduction: Currently, no consensus on optimal renal replacement modality has been reached for end -stage renal disease (ESRD) patients complicated with hemophilia. They may require infusion of coagu-lation factors during each hemodialysis session. In comparison, peritoneal dialysis (PD) might be preferred considering that coagulation replacement is only required for catheter placement. However, limited data on the safety and efficacy of PD for treating ESRD patients with hemophilia were reported.Methods: This is a single-center retrospective cohort study. ESRD patients diagnosed with hemophilia under PD in Peking Union Medical College Hospital from January 1, 1996 to December 31, 2021 were included and followed-up with every month. Their baseline clinical data, catheter insertion procedure, coagulation factor replacement, complications, and outcome were analyzed and compared with general PD patients.Results: In total, 8 patients diagnosed with hemophilia were included, all-male, with a mean age of 50.3 +/- 13.3 years old. Two were acquired hemophilia A, whereas the rest were hereditary hemophilia A (HHA). Seven patients experienced significant hemoglobin (Hgb) increment after PD. Peritoneal hemor-rhage only consisted of a small portion of all hemorrhage. Patients with hemophilia seemed to have lower small solute clearance despite higher baseline peritoneal permeability, and appeared to have increased peritonitis rate than other male PD patients, yet this study is not powered to prove this.Conclusion: PD is a safe and effective choice for patients with hemophilia and ESRD requiring dialysis. More studies are required to evaluate this certain rare group of patients.

BACKGROUND AND AIMS:Liver involvement portends poor prognosis in adults. We aimed to characterize the clinical features, liver function tests, radiologic findings, molecular profiles, therapeutic approaches and outcomes of adults patients with Langerhans cell histiocytosis (LCH) with liver involvement. METHODS:We conducted a retrospective analysis of all adults with LCH (≥ 18 years) seen at Peking Union Medical College Hospital (Beijing, China) between January 2001 and December 2022. RESULTS:Among the 445 newly diagnosed adults with LCH, 90 patients had liver involvement at diagnosis and 22 patients at relapse. The median age was 32 years (range, 18-66 years). Of 112 evaluable patients, 108 had full liver function testing, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), and total bilirubin and albumin. Elevated ALP was seen in 63.0% and GGT in 86.1%; 14.8% had elevated bilirubin. Next-generation sequencing of 54 patients revealed frequent BRAFN486_P490 (29.6%), BRAFV600E (18.5%), and MAP2K1 (14.8%). OUTCOMES:After a median 40 months' follow-up (range 1-168 months), 3-year progression-free survival (PFS) and overall survival were 49.7% and 86.6% respectively. In multivariable analyses, ≥3 abnormal liver function tests (HR 3.384, 95% CI 1.550-7.388, P = .002) associated with inferior PFS; immunomodulatory drug therapy (HR 0.073, 95% CI, 0.010-0.541, P = .010) correlated with superior PFS versus chemotherapy. CONCLUSIONS:In summary, elevated GGT and ALP were common in adults with LCH liver involvement. Greater than equal to 3 abnormal liver function tests predicted poor outcomes. Immunomodulatory drug therapy was associated with favorable progression-free survival compared to chemotherapy.

Understanding the pathobiology of critical illness is essential for patients' prognosis. Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. As part of the host response, procoagulant responses, one of the most primitive reactions in biology, start at the very beginning of diseases and can be monitored throughout the process. Currently, we can achieve near-complete monitoring of the coagulation process, and procoagulant responses serve as indicators of the severity of host response in critically ill patients. However, the rapid interpretation of the complex results of various biomarkers remains a challenge for many clinicians. The indicators commonly used for coagulation assessment are complex, typically divided into three categories for clarity: process index, functional index, and outcome index. Monitoring and understanding these indicators can help manage procoagulant responses. The intervention of procoagulant response should be part of the bundle therapy, alongside the treatment for primary disease, management for hemodynamics, and controlling for host response. Early intervention for procoagulant response mainly includes anti-inflammation, antiplatelet and anticoagulant therapy, as well as management of primary disease. In this review, we systemically introduce the onset, assessment and intervention of procoagulant response.

Background:Multiple trials have confirmed that romiplostim could increase platelet count in individuals with primary immune thrombocytopenia (ITP), but no related study has assessed Chinese patients. Objectives:To assess the effectiveness of romiplostim as a second-line treatment of persistent or chronic ITP in Chinese adults. Methods:This phase III multicenter, randomized, placebo-controlled, double-blind, then open-label clinical trial (NCT02868099, CTR20150395) was conducted at 28 investigational sites in China. The patients were randomly assigned (3:1) to romiplostim (starting and maximum doses of 1 and 10 μg/kg, respectively) or placebo for 9 weeks (double-blind period), followed by the open-label period (both groups administered romiplostim) to week 22. The primary endpoint was the time (in weeks) during which platelet counts were ≥50 × 109/L in the double-blind period. Results:In this study, 202 patients (romiplostim, n = 151; placebo, n = 51) started the treatment. The median (range) numbers of weeks with platelet response after 6 weeks of treatment were 2 (0-6) and 0 (0-2) in patients administered romiplostim and placebo, respectively (P < .001). During the double-blind period, the proportions of patients with treatment-emergent adverse events were comparable between the romiplostim and placebo groups (82.8% vs 82.4%). The treatment-emergent adverse event with ≥10% difference in incidence between these 2 groups was injection site bleeding (1.3% vs 11.8%). Conclusion:Romiplostim significantly increased the time with maintained platelet response in patients with persistent or chronic ITP in comparison with placebo. No new safety signal was observed. Trial registration:ClinicalTrials.gov, NCT02868099. www.chinadrugtrials.org.cn/clinicaltrials.searchlist.dhtml, CTR20150395.

[This corrects the article DOI: 10.1016/j.ekir.2022.09.030.].

Background: Langerhans cell histiocytosis (LCH) is a rare highly heterogeneous histiocytosis, which can be divided into single system(SS) and multiple system(MS) according to clinical site of involvement. There are few studies related to single-system unifocal adult LCH currently. Aims: Objective of this single-center retrospective study is to describe the clinical features, affected organs, gene mutations, treatment and prognosis of adult single-system unifocal LCH patients. Methods: This retrospective study included patients ≥14 years old, and diagnosed with single-system unifocal LCH in Peking Union Medical College Hospital (Beijing, China) from September 2001 to December 2022. Results: Overall 109 patients were enrolled in this study, with a 2.03:1 male to female ratio. Median age at diagnosis was 33 years (14-69). The most common clinical manifestations were bone pain, accounting for 30.3%, followed by cough (11.0%) and diabetes insipidus (11.0%). The most common organs involved were bone (53.2%), followed by lung (18.3%), pituitary (10.1%), lymph nodes (5.5%), skin (2.8%), liver (2.8%) and thyroid (0.9%). Among the 20 patients with lung involvement, 17 patients had smoking history. The frequency of BRAFV600E mutation, MAP2K1 mutation and BRAFindel mutation were 24.3%, 10.8% and 2.7% respectively. BRAFV600Emutations and MAP2K1 mutations were independent of the type of organ involved and were not associated with OS and PFS. As for first-line treatment, 48 had surgery, 15 had radiotherapy, 16 were suggested observation, 9 had chemotherapy. All of the 20 patients with lung involvement were suggested to quit smoking. After a median follow-up time of 43.2 months (0.2-246.6), 3 patients died of respiratory failure, and the estimated 3-year overall survival (OS) was 98.7%. 24 patients developed disease progression, of which 5 had local recurrence, 4 progressed to single system multiple lesions (SS-M) and 15 progressed to MS, and the estimated 3-year progression-free survival (PFS) was 79.0%. Progression rate of pituitary involvement was the highest, 45.5% (5/11), followed by lymph node 33.3% (2/6), lung 20.0% (4/20) and bone 19.0% (11/58) (Figure 1). Univariate analysis showed that patients whose age at diagnosis ≤30 years had significant shorter PFS than those older than 30 years (the estimated 3-year PFS 89.1% vs 66.9%, p =0.039). Summary/Conclusion: In this study, we report a large series of single-system unifocal adult LCH patients. Bone is the most commonly involved organ. The overall survival of single-system unifocal adult LCH is good，and more than 30 years at diagnosis indicate good PFS.Figure1: Progression pattern of each affected organ（N=106） Keywords: Adult, Langerhans Cell Histiocytosis

Background Langerhans cell histiocytosis (LCH) is a rare highly heterogeneous histiocytosis, which can be divided into single system and multiple system disease according to site of involvement. There is a paucity of studies examining unifocal LCH in adults in the molecular era. Results We retrospectively analysed records from 70 patients with unifocal LCH. The median age at diagnosis was 36 years (18–69). The most common organ involved was the bone (70.0%), followed by pituitary gland (7.1%). Target gene sequencing of lesion tissues was performed on 32 of the 70 patients. MAPK/PI3K pathway alterations were observed in 78.1% of the patients; the most common mutations included BRAF V600E (28.1%), MAP2K1 (18.8%) and PIK3CA (9.4%). After a median follow-up time of 39.4 months (0.7–211.8), 10 (14.3%) patients developed disease progression, of whom 4 had local recurrence, 2 progressed to single-system multifocal and 4 progressed to multiple system LCH. The 3-year progression-free survival (PFS) was 81.9%. Univariate analysis showed that age < 30 years at diagnosis was associated with worse 3-year PFS (52.2% vs. 97.0%, p = 0.005). The 3-year overall survival was 100%. Conclusions In our large cohort of adults with unifocal LCH, we found that prognosis of unifocal LCH in adults was very good, and age < 30 years at diagnosis was associated with increased relapse risk.

Click to increase image sizeClick to decrease image size Author contributionsKai-Ni Shen and Xin-Xin Cao contributed to the concept and design of the case report. Kai-Ni Shen and Dan-qing Zhao collected data and drafted the manuscript. Xin-Xin Cao aided in interpretation of clinical data and utilization of specialty specific clinical expertise to critically review and revise the manuscript. All authors critically revised the manuscript and approved the final version.Informed consentWritten informed consent was obtained from the patient included in the study.Disclosure statementNo potential conflict of interest was reported by the author(s).Additional informationFundingThis work was supported by the Beijing Natural Science Haidian frontier Foundation under Grant number L222081; the National High Level Hospital Clinical Research Funding under Grant number 2022-PUMCH-B-046; and the National High Level Hospital Clinical Research Funding under Grant number 2022-PUMCH-A-260.

Renal replacement therapy and perioperative management have difficulties in hemophilia patients with end-stage renal disease. The paper summarized the diagnosis and treatment experience of six hemophilia patients complicated with end-stage renal disease from January 1, 2000 to March 31, 2023 in Peking Union Medical College Hospital. Among 6 patients treated with peritoneal dialysis, 3 were treated with hemodialysis or continuous venous-venous hemodialysis. Altogether 11 dialysis access procedures were conducted successfully, and no serious bleeding or thrombotic events. In further conjunction with literature review, the paper summarized the key points of dialysis access appliance relevant to such patients, to provide reference for renal replacement treatment paths.

Background Langerhans cell histiocytosis (LCH) is a rare, heterogeneous histiocytic disorder. We demonstrated liver involvement at baseline indicated poor survival in adult LCH in our previous study. Aims The aim of this study was to describe clinical features, liver biochemistry, radiology findings, genomic analyses, treatment approaches, and outcomes of adult LCH patients with liver involvement. Methods We conducted a retrospective analysis of all adult LCH patients (≥ 14 years) seen at Peking Union Medical College Hospital (Beijing, China) between January 2001 and December 2022. Liver involvement by one or more of the following: either hepatomegaly, defined as a liver edge greater than 3 cm below the costal margin at the mid clavicular line, or liver dysfunction defined either by abnormal serum biochemical tests including bilirubin greater than 1.5 times the upper limit of normal, alkaline phosphatase (ALP) greater than 1.5 times the upper limit of normal, γ-glutamyl transpeptidase (GGT) greater than 1.5 times the upper limit of normal; or histopathological findings of active disease. Results Among 451 newly diagnosed adult LCH patients, 93 patients had liver involvement at diagnosis and 22 patients had liver involvement at relapse were enrolled, including 80 males (69.6%), and the median age was 32 years (range, 15-66 years). 111 of 115 patients had full liver function test. 70 patients (63.1%) had elevated ALP; 96 patients (86.5%) had elevated GGT, and the median level was 157 U/L (range, 14-2249 U/L); 16 patients (14.4%) had elevated total bilirubin, and the median level was 12.5 umol/L (range, 1.7-248.1umol/L); Among 48 patients who had sufficient DNA for next-generation sequencing, BRAFV600E (20.8%), BRAFN486_P490 (37.5%) and MAP2K1(12.5%) were the most common alternations. In total, 99 patients (86.1%) received first-line systematic treatment, including 76 patients who received chemotherapies (methotrexate/cytarabine regimens, cytarabine monotherapy, vindesine/prednisone-based regimens, cladribine monotherapy and corticosteroid), 15 patients who received immunomodulatory drugs (IMiDs) therapies (thalidomide/cyclophosphamide/dexamethasone regimens and lenalidomide/dexamethasone regimens) and 8 patients who received target therapies (BRAF inhibitors and MEK inhibitors). After a median 39-month follow-up (range 1-168 months), thirteen patients died during follow-up. The estimated 3-year OS rate was 85.5%. 44 patients had disease progression. The median PFS duration was 31.4 months. Nine patients got cirrhosis during follow-up and 2 patients underwent liver transplantation. Univariate analysis was performed to evaluate the prognostic factors of OS and PFS. Patients with elevated total bilirubin at baseline had significantly shorter OS and PFS. Patients who had 3 or more abnormal serum live function tests (including ALT, AST, ALP, GGT, total bilirubin and ALB), and patients with elevated high sensitive C reactive protein (hsCRP) had significantly shorter PFS. Patients who received target therapy or iMIDs-based therapy had significantly longer PFS than patients who received other systemic treatments. In multivariable analyses, Patients who had 3 or more abnormal serum live function tests (HR 2.652, 95% CI 1.256-5.602), and treatment with iMIDs (HR 0.076, 95% CI 0.010-0.564) remained predictive factors for PFS. Conclusion Adult LCH patients with liver involvement most had elevated GGT and ALP. Elevated hsCRP and 3 or more abnormal live function tests predict poor outcomes. Target therapy or iMIDs-based therapy showed better outcomes.